title: Association between inherited CYP2D6/2C19 phenotypes and anticholinergic measures in elderly patients using anticholinergic drugs.
abstract: BACKGROUND
  To compare measures of anticholinergic activity between metabolic phenotypes of the polymorphic enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 in the elderly patients exposed to anticholinergic agents.
  
  
  METHODS
  Long-term nursing home patients (n = 80) with an anticholinergic drug scale (ADS) score ≥3 were recruited from 22 nursing homes in Norway. Based on pharmacogenetic analyses of mutations encoding absent CYP2D6 or CYP2C19 metabolism, patients were divided into subgroups of poor metabolizers (PMs) (n = 8) and extensive metabolizers (n = 72). Serum anticholinergic activity (SAA) was determined by a validated, 96-well format radio receptor assay and adjusted for ADS score. Unadjusted and adjusted SAAs, mouth dryness, and cognitive function (Mini-Mental State Examination and verbal recall tests from Consortium to Establish a Registry for Alzheimer Disease) were compared between the subgroups with Mann-Whitney tests.
  
  
  RESULTS
  The study population was represented by 78% women, 68% had mild to moderate dementia, and mean age was 86 years. More than 80% used more than 1 anticholinergic agent, and their median ADS score was 4. The subpopulation of PMs had significantly higher median SAA than the extensive metabolizers (10.3 versus 4.2 pmol atropine equivalents per milliliter, P = 0.012). This difference remained significant after adjusting for ADS score (P = 0.013). No significant differences in mouth dryness and cognitive function were observed between the subgroups (P > 0.3).
  
  
  CONCLUSIONS
  These preliminary findings suggest that elderly CYP2D6/CYP2C19 PMs with a high anticholinergic drug burden are at increased risk of elevated SAA. Whether PMs are also more prone to experience anticholinergic side effects needs to be further studied in larger patient populations.
authors.affiliation: *Department of Geriatric Medicine, Oslo University Hospital; †Department of Pharmaceutical Services, The Hospital Pharmacies; ‡Institute of Clinical Medicine, University of Oslo; §Department of Pharmaceutical Bioscience, School of Pharmacy, University of Oslo; and ¶Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Kersten
authors.forename: Torgeir B
authors.initials: TB
authors.lastname: Wyller
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009664:Norway; D009735:Nursing Homes; D010597:Pharmacogenetics; D010641:Phenotype; D011869:Radioligand Assay; D018709:Statistics, Nonparametric; D014987:Xerostomia / Q000139:chemically induced
chemical_list: D018680:Cholinergic Antagonists; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6